Effect Of All-trans Retinoic Acid On Matrix Metalloproteinase-9

Objective To investigate the change of matrix metalloproteinase-9(MMP-9) and inflammation in acute lung injury and the effect of all-transretinonic acid(ATRA)，and study the role of ATRA in the therapeutics ofacute lung injury(ALI).Methods SD rats were randomly divided into control, ALI and ATRAintervention groups. The rats in ALI group were administered withvegetable oil by gastric lavage at a dosage of0.5ml/(kg·d),once a day for5d,then injected i.v.with Lipopolysaccharide(LPS) and i.p.with vegetableoil(1ml/kg),while those in ATRA intervention group were administeredwith vegetable oil containing30mg/kg ATRA by gastric lavage at a dosageof0.5ml/(kg·d),once a day for5d,then injected i.v.with LPS and i.p.withvegetable oil(1ml/kg) containing5mg/kg ATRA.however, the rats incontrol group were injected with physiological saline (0.5ml/kg) during thewhole test. The rats in various groups were killed8h after injection i.p.withATRA, and determined for PaO2, the protein content in brochoalveolarlavage fluid(BALF) and the wet/dry(W/D) ratio of lung tissue, observed forlung tissue, and analyzed for expressions of MMP-9mRNA and protein in lung tissue by RT-PCR and immunohistochemcial assay.Results Compared with those in control group, the inflammatorycells in lung tissue of rats with ALI increased significantly,while the PaO2level decreased significantly(P<0.05), and the W/D ratio, protein contentin BALF as well as the expression level of MMP-9mRNA and protein inlung tissue increased significantly(P<0.05or P<0.01). However, comparedwith those in ALI group,the inflammatory reaction in lung tissue of rats inATRA intervention group was relived, while the W/D ratio,proteincongtent in BALF as well as expression level of MMP-9mRNA andprotein in lung tissue decreased significantly (P<0.05or P<0.01), and PaO2level increased significantly(P<0.05)。Conclusion The MMP-9may be participate the inflammation ofALI, ATRA showed curative effect on ALI in rats by a possible mechanismof down-regulation of MMP-9expression.